PROJECT SUMMARY This project will investigate the potential of deep brain stimulation to improve cognitive abilities in aging, and counteract the effects of Alzheimer's and other types of dementias. We will perform experiments in nonhuman primates, because they experience a similar age-related cognitive decline as humans. Stimulation will be applied in the Nucleus Basalis of Meynert, the sole source of acetylcholine to neocortex. Drawing from recent experiments showing success of this method, intermittent stimulation will be delivered at 60 pulses per second for 20 seconds of each minute in old monkeys. The study design will test the efficacy of stimulation, and the duration of benefits after the intervention. Use of complementary pharmacological agents will determine if short-term effects of stimulation on cognition may be augmented by other agents, and what pharmacological systems they interact with. Partial nicotinic acetylcholine receptor agonists, positive allosteric modulators, serotonergic and noradrenergic agents will be tested, as will other agents that interact with cholinesterase inhibitors. In addition, the project will determine whether deep brain stimulation can ameliorate pathological changes associated with Alzheimer's dementias, as noted by biochemical, metabolic, and brain structural measures.